Indomethacin-Dipalmitoylphosphatidylcholine Interaction. A Calorimetric Study of Drug Release from Poly(Lactide-co-glycolide) Microspheres into Multilamellar Vesicles

A comparative study of indomethacin controlled release from poly(lactide-co-glycolide) (50:50, molecular weight 3000) (PLGA) microspheres loaded with two different amounts of drug (10.9 ± 1%, and 34.1 ± 1% w/w) and pure free indomethacin, considering the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine multilamellar vesicles, was carried out by differential scanning calorimetry (DSC). The release was monitored by comparing the effect exerted by the free indomethacin on lipid thermotropic behavior with that of the drug released by the microspheres and relating these effects to a lipid aqueous dispersion containing the molar ratio of drug able to cause it. By DSC measurements, the pure free indomethacin was found to be able to have a fluidifying effect on the model membrane, causing a shift toward lower values of the transitional temperature (T_m), characteristic of phospholipid liposomes, without variations in the enthalpic changes (ΔH). This shift was found to be modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Successively, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and indometha-cin-loaded microspheres as well as free powdered indomethacin, and the T_m shifts of the lipid bilayer caused by the drug released from the polymeric system, as well as by the free drug, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This drug release model could be employed to determine the different kinetics involved in the drug transfer from the microspheres to a membrane. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres. This calorimetric study shows that the PLGA microspheres are a good delivery system able to sustain drug release. Moreover, the DSC technique applied to the drug interaction with biomembranes constitutes a good tool for determining the drug release representing an innovative alternative in vitro model.     

Drug resistance in the fission yeast Schizosaccharomyces pombe: pleiotropic mutations affecting the oleic acid and sterol composition of cell membranes

Summary The whole cell lipid and sterol content of the drug resistant strains cyh1, cyh3 and cyh4 was compared with that of wild type by thin layer and gas liquid chromatography and by UV spectrophotometric analysis. The cyh3 and cyh4 strains had a decreased content of the unsaturated 18:1 fatty acid oleic acid, a decreased content of ergosterol and an increased content of 24,28 dehydroergosterol with respect to wild type. The cyh1 strain, however, only showed a decreased content of ergosterol and an increased content of 24,28 dehydro-ergosterol when compared to wild type.     

心肌缺血／再灌注损伤时相性变化的电子示踪研究

本文以结扎家兔冠状动脉左室支为心肌缺血模型,应用镧电子示踪技术,生物体视学定量分析等方法,观察了心肌缺血不同时间再灌注后细胞膜系及线粒体超微结构以及镧示踪所提示的线粒体的功能变化等特点。结果表明,在心肌缺血20分时,细胞膜通透性升高,镧粒子进入细胞,再灌注时更为严重,即出现再灌注损伤。此时镧粒子多集于肌浆管。随缺血时间延长(30—40分),变化愈趋严重,缺血40分后再灌注,镧粒子大量涌入线粒体。而缺血60分,特别是再灌注时,心肌细胞严重破坏,几乎无完整线粒体,其中亦很少有镧颗粒。说明在此情况下的再灌损伤已属不可逆性。膜通透性的变化是由外及里的,即先肌膜而后为细胞内膜。就线粒体来讲则是先外膜而后内膜。实验结果提出可逆性(早期)再灌注损伤期,及不可逆性再灌注损伤期(晚期)的概念。     

Membranes for endotoxin removal from dialysate: considerations on feasibility of commercial ceramic membranes

As the quality of water in dialysis fluid varies considerably, dialysate is often contaminated by large amounts of bacteria and endotoxins. Membrane properties and operating pressures are acknowledged to give high-flux dialysis with bicarbonate the bacteriological potential to favor passage of endotoxin fragments from the dialysate into the blood stream. Therefore, a sterile dialysate will have to become a standard. Ultrafiltration across hydrophobic synthetic membranes was shown to remove endotoxins (and their fragments) from dialysis water by the combined effect of filtration and adsorption. However, each module can be used for a limited time only. Ceramic membranes may represent an alternative to polymeric membranes for endotoxin removal. In this article, we tested the capacity of different commercial ceramic membranes with nominal molecular weight cut-off down to 1,000 to retain endotoxins from Ps. aeruginosa. The tested membranes did not generally produce dialysate meeting the Association for the Advancement of Medical Instrumentation standard. When using aluminum-containing membranes, we detected aluminum leaking into the dialysate that could possibly be transported into the blood stream.     

Is membrane sweeping beneficial at the initiation of labor induction?

Objective: To determine whether cervical membrane sweeping during labor induction is beneficial.

Methods: Outcomes of labor after induction in pregnant women at term were compared in a randomized trial. Women were assigned to having their membranes “swept” or “not swept” at the initiation of labor induction.

Results: We recruited a total of 870 women of which 70 were excluded. There were 400 nullipara (Group A) [198 “swept”, 202 “not swept”] and 400 multiparas (Group B) (201 “swept” and 199 “not swept”]. Among group A who received intravaginal prostaglandin (PG) E₂, those who had simultaneous sweeping had significantly shorter mean induction-labor interval (12.9?±?1.3 versus 16.2?±?1.1 hours, p?=?0.046), lower mean dose of oxytocin (6.6?±?0.6 versus 10.11?±?1.4?mU/minute, p?=?0.01), and increased normal delivery rates (vaginal delivery 82.8% versus 58.6%, p?=?0.01). Sweeping also had a favorable effect on nulliparas who had ARM and received oxytocin alone (mean induction-labor interval 5.9?±?2.9 versus 10.9?±?2.6 hours p?=?0.04, mean maximum dose of oxytocin 9.8?±?1.1 versus 15.2?±?1.1?mU/min, p?=?0.01). These results were restricted to women with unfavorable cervix in Group A those who had membrane sweeping.

Conclusion: Membrane sweeping, has beneficial effects on labor and delivery, which is limited to nulliparas with unfavorable cervix requiring PGE₂ or Oxytocin alone.     

A Simplified Method for Measuring the Thickness of Glomerular Basement Membranes

Measurement of the thickness of glomerular basement membranes is required for the diagnosis of thin membrane nephropathy. Over the years various morphometric methods have been used but some are laborious so there is a need for establishing a simplified method for measuring thickness. In the present study 20 renal biopsies were used to carry out a comparative morphometric analysis between 2 methods. The first method was based on measuring thickness at the maximum number of available points, whereas for the second method, thickness was measured at only 5 points per loop. Since both methods gave mean values that are not statistically different in each patient, the authors recommend that the simplified method be used routinely for diagnosis.     

胎膜早破的护理

目的探讨胎膜早破的临床表现及发生因素,以采取针对性措施减少对母婴的危害。方法对618例胎膜早破病例进行回顾性分析,针对病因和临床表现,进行预防和护理。结果618例胎膜早破产妇无1例发生产褥感染,新生儿无1例发生新生儿感染及死亡。结论认真做好产前检查、纠正胎位、针对病因治疗,可预防或减少胎膜早破的发生;对已出现胎膜早破者应给予积极治疗和适当的护理,适时终止操作可减少婴儿并发症的发生。     

Polyetherimide: a new membrane-forming polymer for biomedical applications

Membranes for biohybrid organs such as the biohybrid liver support system have to face 2 different environments, namely blood and tissue cells. Accordingly, the respective membrane surfaces must have optimal properties in terms of biocompatibility for blood or tissue. Flat membranes prepared by a phase inversion process from polyetherimide were modified by binding of tris-(hydroxymethyl)-aminomethane to obtain a surface with hydroxyl groups by binding of polyethylene imine to attach a hydrophilic macromolecule with amine groups useful as a spacer for later bonding of further ligands and by attachment of heparin. The binding of the different ligands was successful as monitored by different physicochemical methods. The blood response of plain polyetherimide was comparable to that of polyacrylonitrile, and it could be further improved by the binding of heparin. The tissue compatibility of polyetherimide and its different modifications was compared with commercial cell culture substrate membranes (Millicell) and found to be comparable for polyetherimide and even better after the modification with tris-(hydroxymethyl)-aminomethane. In conclusion, polyetherimide seems to be an interesting material for the production of membranes for application in biohybrid organ systems.     

A calorimetric study on diflunisal release from poly(lactide-co-glycolide) microspheres by monitoring the drug effect on dipalmitoylphosphatidylcholine liposomes: temperature and drug loading influence

Diflunisal release from poly-Lactide-co-Glycolide (50:50, 34,000 MW) microspheres loaded with two different amounts of drug (2.5 +/- 0.5% and 10 +/- 0.5% w/w) was monitored by following the effects exerted by the drug on the thermotropic behavior of dipalmitoylphosphatidylcholine unilamellar vesicles at different temperatures. The effects of the drug released from the microspheres on the thermotropic behavior of lipid aqueous dispersion containing different molar ratios of drug was detected by differential scanning calorimetry and was compared with the effects exerted by the free Diflunisal. Diflunisal affects mainly the temperature (T_m) of the transition characteristic of phospholipid vesicles as model biomembrane, causing a shift toward lower values. This shift was modulated by the drug molar fraction with respect to the lipid concentration in the aqueous dispersion. Afterward, calorimetric measurements were performed on suspensions of blank liposomes added to weighed amounts of unloaded and differently Diflunisal-loaded microspheres as well as free powdered Diflunisal after incubation for increasing times at three different temperatures (25, 37, and 50°C). The T_m shifts of the lipid bilayer, caused by the drug released from polymeric system as well as by the free drug during incubation periods, were compared with that caused by free drug increasing molar fractions dispersed directly on the membrane, employed as a calibration curve to obtain the fraction of drug released. This in vitro study suggests that the kinetic process involved in drug release is influenced by the amount of drug loaded in the microspheres as well as by the temperature acting on drug solubility and membrane disorder. This drug release model, monitored by the calorimetric technique shows that a) the poly-Lactide-co-Glycolide microspheres are a good delivery system able to sustain the drug release; b) the differential scanning calorimetry technique applied on the drug interaction with biomembranes constitutes a good tool to follow the drug release; 3) this model, representing an innovative alternative in vitro model, should be used to determine the different kinetics involved in the drug transfer from a drug delivery system to a membrane as uptake site.     

复方654—2膜剂治疗顽固性小腿慢性溃疡

我们研制的654-2膜剂是以654—2、氯霉素为主药,通过其扩张微血管,改善微循环、抑菌、消炎,促进肉芽上皮生长等作用,外敷治疗顽固性小腿慢性溃疡,取得明显的疗效。溃疡愈合时间短,平均三周,无需口服、肌注抗生素,且操作简单方便,付作用轻微,本文就治疗方面有关问题进行讨论。